Biosynthesis of isocitric acid in repeated-batch culture and testing of its stress-protective activity

• Published in: Applied microbiology and biotechnology 2019-04, Vol.103 (8), p.3549-3558
• Main Authors: Morgunov, Igor G., Kamzolova, Svetlana V., Karpukhina, Olga V., Bokieva, Svetlana B., Inozemtsev, Anatoly N.
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Antioxidants; Applied Microbial and Cell Physiology; Batch culture; Biomedical and Life Sciences; Biosynthesis; Biotechnology; Carboxylic acids; Cultivation; Culture; Ethanol; Heavy metals; Isocitric acid; Learning; Life Sciences; Methods; Microbial Genetics and Genomics; Microbiology; Molybdenum; Neurotoxicity; Oxidative stress; Pharmacology; Salts; Stress (Physiology); Testing; Yarrowia lipolytica; Yeast
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-019-09729-8

Biosynthesis of Ds(+)-threo-isocitric acid from ethanol in the Yarrowia lipolytica batch and repeated-batch cultures was studied. Repeated-batch cultivation was found to provide for a good biosynthetic efficiency of the producer for as long as 748 h, probably due to maintenance of high activities of enzymes involved in the biosynthesis of isocitric acid. Under optimal repeated-batch cultivation conditions, the producer accumulated 109.6 g/L Ds(+)-threo-isocitric acid with a production rate of 1.346 g/L h. The monopotassium salt of isocitric acid isolated from the culture liquid and purified to 99.9% was found to remove neurointoxication, to restore memory, and to improve the learning of laboratory rats intoxicated with lead and molybdenum salts. Taking into account the fact that the neurotoxic effect of heavy metals is mainly determined by oxidative stress, the aforementioned favorable action of isocitric acid on the intoxicated rats can be explained by its antioxidant activity among other pharmacological effects.